chr7-19117047-CCGCCGCCGCCGCCCG-C
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM1BS2
The NM_000474.4(TWIST1):c.260_274delCGGGCGGCGGCGGCG(p.Ala87_Gly91del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000108 in 1,398,748 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00031 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 7 hom. )
Consequence
TWIST1
NM_000474.4 disruptive_inframe_deletion
NM_000474.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.49
Genes affected
TWIST1 (HGNC:12428): (twist family bHLH transcription factor 1) This gene encodes a basic helix-loop-helix (bHLH) transcription factor that plays an important role in embryonic development. The encoded protein forms both homodimers and heterodimers that bind to DNA E box sequences and regulate the transcription of genes involved in cranial suture closure during skull development. This protein may also regulate neural tube closure, limb development and brown fat metabolism. This gene is hypermethylated and overexpressed in multiple human cancers, and the encoded protein promotes tumor cell invasion and metastasis, as well as metastatic recurrence. Mutations in this gene cause Saethre-Chotzen syndrome in human patients, which is characterized by craniosynostosis, ptosis and hypertelorism. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM1
In a chain Twist-related protein 1 (size 201) in uniprot entity TWST1_HUMAN there are 64 pathogenic changes around while only 11 benign (85%) in NM_000474.4
BS2
High AC in GnomAd4 at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TWIST1 | NM_000474.4 | c.260_274delCGGGCGGCGGCGGCG | p.Ala87_Gly91del | disruptive_inframe_deletion | Exon 1 of 2 | ENST00000242261.6 | NP_000465.1 | |
TWIST1 | NR_149001.2 | n.575_589delCGGGCGGCGGCGGCG | non_coding_transcript_exon_variant | Exon 1 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TWIST1 | ENST00000242261.6 | c.260_274delCGGGCGGCGGCGGCG | p.Ala87_Gly91del | disruptive_inframe_deletion | Exon 1 of 2 | 1 | NM_000474.4 | ENSP00000242261.5 | ||
TWIST1 | ENST00000354571.5 | n.56_70delCGGGCGGCGGCGGCG | non_coding_transcript_exon_variant | Exon 1 of 3 | 2 | ENSP00000346582.5 | ||||
TWIST1 | ENST00000443687.5 | n.-140_-126delCGGGCGGCGGCGGCG | upstream_gene_variant | 4 | ENSP00000416986.1 |
Frequencies
GnomAD3 genomes AF: 0.000307 AC: 46AN: 149952Hom.: 1 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
46
AN:
149952
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Cov.:
32
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GnomAD2 exomes AF: 0.000365 AC: 18AN: 49264 AF XY: 0.000309 show subpopulations
GnomAD2 exomes
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18
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49264
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GnomAD4 exome AF: 0.0000841 AC: 105AN: 1248688Hom.: 7 AF XY: 0.0000848 AC XY: 52AN XY: 613002 show subpopulations
GnomAD4 exome
AF:
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105
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1248688
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52
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613002
Gnomad4 AFR exome
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56
AN:
24878
Gnomad4 AMR exome
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AC:
5
AN:
15596
Gnomad4 ASJ exome
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0
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18702
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1
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28164
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2
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55772
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0
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31140
Gnomad4 NFE exome
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AC:
36
AN:
1018118
Gnomad4 Remaining exome
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AC:
4
AN:
51320
Heterozygous variant carriers
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18
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GnomAD4 genome AF: 0.000307 AC: 46AN: 150060Hom.: 1 Cov.: 32 AF XY: 0.000232 AC XY: 17AN XY: 73240 show subpopulations
GnomAD4 genome
AF:
AC:
46
AN:
150060
Hom.:
Cov.:
32
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AC XY:
17
AN XY:
73240
Gnomad4 AFR
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AC:
0.00101484
AN:
0.00101484
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AC:
0.0000661726
AN:
0.0000661726
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0
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0
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AC:
0.000203915
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0.000203915
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0
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0.0000297124
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0.0000297124
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0
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0
Heterozygous variant carriers
0
3
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16
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
Mutation Taster
=174/26
disease causing (fs/PTC)
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at